P502: PHASE II STUDY ON VENETOCLAX PLUS DECITABINE FOR ELDERLY (≥60 &lt;75YEARS) PATIENTS WITH NEWLY DIAGNOSED HIGH-INTERMEDIATE RISK AML ELEGIBLE FOR ALLO-SCT: MIDTERM UPDATE OF VEN-DEC GITMO STUDY
Authors: Domenico Russo, Nicola Polverelli, Marika Vezzoli, Stella Santarone, Luca Castagna, Francesco Onida, Stefania Bramanti, Roberto Sorasio, Angelo Michele Carella, Attilio Olivieri, Calogero Vetro, Germana Beltrami, Antonio Curti, Massimo Stefano Luca Bernardi, Valentina Mancini, Pellegrino Musto, Elisabetta Terruzzi, Piero Galieni, Cristina Skert, Luisa Giaccone, Raffaella Cerretti, Erika Borlenghi, Mirko Farina, Alessandro Leoni, Simona Bernardi, Stefano Calza, Angela Gheorghiu, Michele Malagola, Massimo Martino, Fabio Ciceri
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Allogeneic stem cell transplantation (allo-SCT) represents the preferred consolidation treatment for patients affected by intermediate/high risk ELN acute myeloid leukemia. Unfortunately, due comorbidities and unfitness to intensive chemotherapy only a minority of elderly patients (aged ≥60) may benefit of such a curative approach. Aims: VEN-DEC GITMO trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the safety and efficacy of the “chemo-free” combination Venetoclax plus Decitabine (VEN-DEC) as “bridge” to allo-SCT in elderly (≥ 60 - < 75 years) AML patients. Methods: Venetoclax and Decitabine were administered for 2 cycles and then response was evaluated. In case of CR/CRi/MLFS (hereinafter defined as CR) according to ELN criteria, patients had to undergo allo-SCT within 2 months. In case of NR or PR after the 2nd Cycle VEN-DEC, 2 additional cycles had to be administered and patients achieving CR had to undergo allo-SCT within 2 months. Patients with NR or PR went off the study and could be treated according to single center policy. The study was designed as a Simon optimal two-Stage Phase II clinical trial, including a planned futility check. Considering an overall 12% of drop-out rate, a total of 100 patients had to be enrolled. Primary objective is the proportion of elderly AML patients who receive allo-SCT in CR with the “chemo-free” combination VEN-DEC. According to the statistical plan, primary endpoint was met in case of more than 15% of patients in CR submitted to allo-SCT. Figure 1 illustrates the study design. Results: The study started at July 2021 and, as expected, 100 patients were enrolled at December 2022 by 25 Italian Gitmo Transplant Centers. Data cut-off is February 18th, 2023. Screening failure was registered in 6 pts (6%), all the remaining 94 pts started the 1st cycle of treatment, 75 pts completed the 2nd cycle of VEN-DEC and were evaluable for treatment response. Overall, CR was recorded in 49 patients after 2 cycles (65.3%), partial or non-response in 26 cases. Four out of 26 (15%) PR/NR patients obtained a CR after 2 additional cycles of therapy. A total of 37 and 12 patients received a third and/or a fourth cycle of treatment after reaching a CR after cycle 2 while waiting for transplant, due to logistical issues. According to study protocol, first cycle was administered inpatient in all patients. Cycle 2 was given outpatient in 74% of cases. Median time to response was 67 days (range, 49-175). A total of 8/94 (9%) patients have died before transplant (in 3 cases for disease progression). At data cut-off, 41/94 (43.6%) patients have been successfully undergone allo-SCT and 12 patients are awaiting for transplant. Summary/Conclusion: Even if the study is still ongoing, the primary endpoint has already been met. Final analysis is planned at end of May 2023 before EHA meeting. In that report, comprehensive evaluation of efficacy and toxicity will be reported. Acknowledgement Monica Bonzi, Sr. Clinical Lead - IQVIA RDS, Italy.Keywords: Venetoclax, Acute leukemia, Induction chemotherapy, decitabine